The Food and Drug Administration (FDA) has granted approval to two drugs targeting metastatic non-small cell lung cancer.

Capmatinib (Tabrecta) has been approved for the treatment of metastatic non-small cell lung cancer in adults whose tumors have a mutation leading to mesenchymal-epithelial transition (MET) exon 14 skipping. This genetic variation must be detected by an FDA-approved test.

Capmatinib is a kinase inhibitor targeting MET (including the mutant variant produced by exon 14 skipping). MET signaling has important roles in cell motility, proliferation, embryogenesis, organogenesis, liver regeneration, and wound healing.1 MET exon 14 skipping results in a protein with a missing regulatory domain, leading to increased MET signaling and increased cancer cell growth. Capmatinib inhibits cancer cell growth driven by the mutant MET variant lacking exon 14. About 3% of patients with non-small cell lung cancer have the MET exon 14 skipping variant.

In 2020, capmatinib received accelerated approval for this indication based on initial overall response rate and duration of response from a multicenter, nonrandomized, open-label, multicohort study. Full approval was granted after the manufacturer, Novartis, submitted additional data from 63 patients, as well as data from an additional 22 months of follow-up during which duration of response and clinical benefit were assessed.

The product's labeling warns of several serious adverse effects, including interstitial lung disease/pneumonitis, which can be fatal; hepatotoxicity (indicated by elevated alanine aminotransferase, aspartate aminotransferase, and bilirubin levels); pancreatic toxicity (measured by elevated amylase and lipase levels); photosensitivity; and embryo-fetal toxicity. The most common adverse effects include edema, nausea, musculoskeletal pain, fatigue, vomiting, dyspnea, cough, and decreased appetite.

Capmatinib is taken orally twice a day. Nurses should teach patients to swallow the medication whole without crushing or chewing the tablets. Patients should be informed that laboratory values will need to be monitored throughout therapy to detect changes in liver and pancreatic function. Specific dosage modifications based on the severity of adverse effects are delineated in the drug's labeling. Patients should be taught to limit their direct ultraviolet light exposure while on capmatinib to decrease the risk of photosensitivity reactions. Patients of reproductive age, or who have partners of reproductive age, should use birth control while taking capmatinib.

For complete prescribing information for capmatinib, go to http://www.accessdata.fda.gov/drugsatfda_docs/label/2022/213591s004lbl.pdf.

Fam-trastuzumab deruxtecan-nxki (Enhertu). The FDA has granted accelerated approval to fam-trastuzumab deruxtecan-nxki (Enhertu) for the treatment of unresectable or metastatic non-small cell lung cancer in adults whose tumors have activating human epidermal growth factor receptor 2 (HER2) mutations and who have received prior systemic therapy. This mutation must be detected by an FDA-approved test prior to drug administration.

Enhertu is the first drug approved for HER2-mutant non-small cell lung cancer. In May, the drug was approved for the treatment of unresectable or metastatic HER2-positive breast cancer in adults who received a prior anti-HER2-based regimen. It was also approved in 2019 for the treatment of locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma in adults who received a prior trastuzumab-based regimen.

Enhertu's efficacy in treating non-small cell lung cancer was determined in a multicenter, multicohort, randomized, blinded, dose-optimization trial of 52 eligible patients. Additional clinical studies to verify and describe the drug's clinical benefit may be needed for full approval.

Enhertu carries a boxed warning regarding the risk of interstitial lung disease and embryo-fetal toxicity. The most common adverse effects include laboratory abnormalities (decreases in white blood cell counts, hemoglobin, neutrophil counts, lymphocyte counts, platelet counts, and albumin; and increases in aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase), gastrointestinal symptoms (nausea, constipation, decreased appetite, and vomiting), fatigue, and alopecia.

Because of the risk of interstitial lung disease and pneumonitis, which can be fatal, nurses should carefully assess for and immediately report signs and symptoms such as cough, dyspnea, fever, or other new or worsening respiratory symptoms. Patients should report these respiratory symptoms to their prescriber immediately.

Nurses should premedicate patients with prophylactic antiemetic medications for the prevention of chemotherapy-induced nausea and vomiting. If infusion reactions are noted, nurses should slow or interrupt the infusion rate; severe infusion reactions may require permanent discontinuation of Enhertu.

To prevent a medication error, nurses should be aware that there are generic names for other drugs that are similar to the generic name for Enhertu. When administering Enhertu, nurses should confirm that the drug is fam-trastuzumab deruxtecan-nxki and not trastuzumab or ado-trastuzumab emtansine. Enhertu is considered a hazardous drug, so nurses should closely follow guidelines for handling and disposal. The drug should be reconstituted immediately before dilution.

Because of the risk of embryo-fetal toxicity, patients of childbearing age, or who have partners of childbearing age, should use effective contraception during treatment and for up to seven months after the last dose. Animal toxicity studies suggest that men may have impaired fertility due to Enhertu therapy and male patients should be aware of this risk.

For complete prescribing information for Enhertu, go to http://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761139s021lbl.pdf.

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